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ATL: A Morphologic and Molecular Correlation Study
  1. Jinjun Xiong, MD*,
  2. Mai He, MD, PhD*,
  3. Cynthia Jackson, PhD,
  4. Joyce J. Ou, MD, PhD*,
  5. C. James Sung, MD*,
  6. Virgina Breese, BS,
  7. Margaret M. Steinhoff, MD*,
  8. M. Ruhul Quddus, MD*,
  9. Trevor Tejada-Berges, MD and
  10. W. Dwayne Lawrence, MD*
  1. *Department of Pathology, Women & Infants Hospital of Rhode Island, Brown University,
  2. Molecular Laboratory, Department of Pathology, Rhode Island Hospital, Brown University, and
  3. Department of Obstetrics and Gynecology, Women & Infants Hospital of Rhode Island, Brown University, Providence, RI.
  1. Address correspondence and reprint requests to Jinjun Xiong, MD, Department of Pathology, Women & Infants Hospital of Rhode Island, 101 Dudley St, Providence, RI 02905. E-mail: jxiong{at}wihri.org.
  1. A portion of the results has been presented at the USCAP Annual Meeting in San Antonio, Texas, in March, 2011.

Abstract

Objectives K-ras gene product in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway is critical in the development of certain types of malignancies. K-ras mutation–associated pancreatic and ovarian carcinomas often display mucinous differentiation. Previous studies have shown that k-ras mutation is found in 10% to 30% of endometrial carcinomas. We investigated k-ras mutations in several morphologic subtypes of endometrial carcinomas with particular emphasis on various degrees of mucinous differentiation.

Methods Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Polymerase chain reaction amplification for k-ras codons 12 and 13 were performed, followed by sequencing using capillary electrophoresis. The Fisher exact test is used to compare the prevalent difference of k-ras mutation among the groups. P < 0.05 was considered significant.

Results K-ras mutations were detected in 8 (80%) of 10 mucinous carcinomas, 12 (67%) of 18 endometrioid carcinomas (ECs) with significant mucinous differentiation (ECMD), 4 (25%) of 16 ECs, and 1 (9%) of 11 serous carcinomas. The differences were statistically significant between mucinous carcinomas versus EC (P < 0.01) and ECMD versus EC (P < 0.05).

Conclusion The findings suggest that mucinous carcinoma and endometrioid carcinoma with significant mucinous component are more likely to be associated with k-ras mutation. Potential clinical implications of k-ras mutation lies in the management of recurrent or higher-stage endometrial mucinous tumors, which would not be responsive to treatment protocols containing epidermal growth factor receptor inhibitors.

  • Endometrial carcinoma
  • Mucinous differentiation
  • K-ras mutation
  • DNA sequencing

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Footnotes

  • This work was supported in part by a pilot project fund from the Department of Pathology, Warren Alpert Medical School of Brown University.

  • The authors declare no conflicts of interest.

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